School of Medicine

The effects of activating mutations in HRAS, BRAF, and MEK1 were examined on human hair. We found that all three mutations induced a tightly curled morphology. Histologic and scanning electron microscopy analysis revealed the tightly curled phenotype of cardiofaciocutaneous syndrome hair to be indistinguishable from normal tightly curled hair. No differences were detected in Costello syndrome hair compared to normal tightly curled hair, except for greater variety of cross sectional shape; however, this analysis was limited to a single sample. These findings suggest that the normal curled phenotype of human hair could be caused by increased RAS/RAF signaling. Although the alleles of RAS/MAPK syndrome patients vary in strength, curly hair development may respond after a signaling threshold is reached. It may be possible to predict specific phenotypes in humans experiencing excess or insufficient RAS/RAF signaling. Further efforts are ongoing to identify whether there are normal genetic variants in humans that affect RAS/MAPK signaling and hair morphology.